An Open-Label, Randomized Phase I Study in Healthy Adults of the Safety and Immunogenicity of Prime-Boost Intervals with Monovalent Influenza Subunit Virion (H5N1) Vaccine, A/Indonesia/05/2005 (Sanofi Pasteur, Inc), Administered Alone or Following Recombinant DNA Plasmid (H5) Vaccine, VRC-AVIDNA036-00-VP (VRC, NIAID)
Study Design:
This is a Phase I, randomized, open-label study to evaluate the safety, tolerability, and immunogenicity of prime-boost vaccination regimens against the influenza virus hemagglutinin H5. One group will receive A/Indonesia/05/2005 (inactivated H5N1) vaccine as both prime and boost, and the other groups will receive the VRC-AVIDNA036-00-VP (DNA) vaccine as prime with inactivated H5N1 boost but with various boost intervals. The VRC 310 study will provide data from different prime-boost schedules to identify whether homologous or heterologous schedules result in a better antibody response as well as which interval of time between vaccinations is associated with the best immune response. The hypothesis is that all of the study regimens will be safe for human administration and will elicit antibody and T cell responses against the H5 protein. The primary objectives are to evaluate the safety and tolerability of the investigational vaccine regimens, at a dose of 4 mg for the DNA vaccine and 90 microg for the inactivated H5N1, in healthy adults. Secondary and exploratory objectives are related to the immunogenicity of the study vaccine regimens and identification of an interval between prime and boost that has the highest frequency of strong immune responses.
Product Description:
The inactivated H5N1 vaccine is monovalent subunit virion vaccine, A/Indonesia/05/2005 clade 2, manufactured by Sanofi Pasteur, Inc (Swiftwater, PA). Vaccine vials will be supplied at 90 microg/0.5mL. The VRC-AVIDNA036-00-VP vaccine was developed and manufactured by VRC, NIAID and is composed of a single closed-circular DNA plasmid that encodes the H5 protein with a CMV/R promoter. Vaccine vials will be supplied at 4 mg/mL. Each vaccination will be administered intramuscularly (IM) in the deltoid muscle using needle and syringe for the H5N1 vaccine and the Biojector 2000 Needle-Free Injection Management System (Biojector) for the DNA vaccine.
Subjects:
A total of 60 healthy adults, ages 18-60 years will be enrolled.
Study Plan:
Subjects will be simultaneously randomized equally into one of 6 groups. Subjects and clinicians will be blinded to group assignment until Day 0 following completion of the enrollment. At the point of enrollment the randomly assigned regimen will become known to subjects and clinicians. Subjects will receive two injections on the schedule shown in the schema. The protocol requires 5 or 6 clinic visits, depending upon the group, and telephone follow-up contact after the first study injection and 24 weeks after the second study injection. Additional optional visits may be conducted at study weeks 48 and 72 to collect blood for evaluation of immune response durability.
Study Duration:
Each participant will complete clinical follow up through 24 weeks after the second vaccination. Duration of the expected time on study will vary from 28 to 48 weeks depending upon the Group, but may be extended to 72 weeks after enrollment for subjects who agree to complete the optional research blood drawas.
